A Straightforward and General Strategy Towards 1,5‐Dithio‐1‐enopyranosides

Abstract

The synthesis of a new class of thiosugar derivatives, 1,5-dithio-1-enopyranosides, has been achieved in a two-step sequence from easily available aldofuranoses. In the first step, a carbohydrate-derived ketene dithioacetal was formed by Peterson olefination of an aldofuranose and a lithiated α-silyl thioacetal. In the second step, intramolecular nucleophilic

Synthesis of 2‐Substituted Thioglycals from Carbohydrate‐Derived Ketene Dithioacetals

“…First, we were interested in a previously reported method dealing with an efficient synthesis of glycals by reaction of glycosyl sulfoxides and organolithium reagents . Investigations on the selective oxidation of the sulfur atoms of the ketene dithioacetal function were undertaken using model starting material 1 prepared as described previously . The best results were determined using a stoichiometric amount of m ‐CPBA as the oxidant in dichloromethane.…”

“…For the introduction of electrophilic groups at C‐2 of thioglycal 3 , path B was then studied (Scheme ). Indeed, in a previous paper, we reported an easy and efficient substitution at the double bond of the enantiomer of ketene dithioacetal 1 with an electrophilic species generated in situ (Scheme ) …”

“…After a careful NMR study, the structures were established as a mixture of endocyclic sulfonium 4 and exocyclic sulfonium 5 indicating that alkylation occurred at the sulfur atom (Scheme ). Compound 4 was obtained as a mixture of two diastereoisomers, the major one featuring the methyl substituent on the opposite side of the isopropylidene group ( R configuration at the sulfur atom) by analogy with our previous work …”

“…Solvents used for reactions, were commercially available (dimethylformamide) or dried using a Pure Solv solvent drying system (Innovative Technology) over aluminum oxide under an argon atmosphere before use (dichloromethane, tetrahydrofuran, diethyl ether). Cyclic ketene dithioacetal 1 was prepared as described previously in four steps from d ‐arabinose . Togni's reagent and Selectfluor were purchased from Innov'Orga company (Reims, France).…”

“…Some years ago, we have reported a straightforward and general strategy towards the preparation of 1,5‐dithio‐1‐enopyranosides in a two‐step sequence from easily available protected aldofuranoses (Scheme ) …”